REVERSIBLE TRANSDIFFERENTIATION OF ALVEOLAR EPITHELIAL-CELLS

Alveolar epithelial type II (AT2) cells have been thought to be the pr ogenitors of terminally differentiated type I (AT1) cells in the adult animal in vivo. In this study, we used an AT1 cell-specific monoclona l antibody (mAb VIII B2) to investigate expression of the An cell phen otype accompanying reversible changes in expression of the AT2 cell ph enotype. AT2 cells were isolated and cultured either on attached colla gen gels or on gels detached 1 or 4 days after plating and maintained thereafter as floating gels. Monolayers on both attached and floating gels were harvested on days 4 and 8 and analyzed by electron microscop y for changes in morphology and binding of mAb VIII B2. Results indica te that: (1) alveolar epithelial cells (AEC) on attached gels develop characteristics of the AT1 cell phenotype, (2) AEC on gels detached on day 1 maintain features of the AT2 cell phenotype (and do not react w ith mAb VIII B2), and (3) the expression of ATI cell phenotypic traits seen by day 4 on attached gels is reversed after detachment. We concl ude that commitment to the AT1 and AT2 cell lineages requires continuo us regulatory input to maintain the differentiated states, and that tr ansdifferentiation between AT2 and AT1 cells may be reversible.